Neobavaisoflavone May Modulate the Activity of Topoisomerase Inhibitors towards U-87 MG Cells: An In Vitro Study

Despite many advances in therapy, glioblastoma (GB) is still characterized by its poor prognosis. The main reason for this is unsuccessful treatment, which slightly extends the duration of remission; thus, new regimens are needed. One of many types of chemotherapeutics that are being investigated in this field is topoisomerase inhibitors, mainly in combination therapy with other drugs. On the other hand, the search for new anti-cancer substances continues. Neobavaisoflavone (NBIF) is a natural compound isolated from Psoralea corylifolia L., which possesses anti-oxidant, anti-inflammatory, and anti-cancer properties. The aim of this study was to evaluate the effect of NBIF in human U-87 MG glioblastoma cells in comparison to normal human NHA astrocytes, and to examine if it influences the activity of irinotecan, etoposide, and doxorubicin in this in vitro model. We demonstrated that NBIF decreases U-87 MG cells viability in a dose-dependent manner. Furthermore, we found that it inhibits cell growth and causes glutathione (GSH) depletion more intensely in U-87 MG cells than in astrocytes. This study also provides, for the first time, evidence of the potentialization of the doxorubicin effect by NBIF, which was shown by the reduction in the viability in U-87 MG cells.     

高效液相色谱法测定人血清中鬼臼乙叉甙浓度

建立了测定血清中鬼臼乙叉甙浓度的反相高效液相色谱方法。血清样品以乙酸乙酯提取,加表鬼臼毒噻吩糖甙作内标,以甲醇∶水（５５∶４５）为流动相,紫外２５４ｎｍ检测,最低检测浓度０．１ｍｇ／Ｌ,在药物浓度为０．５～５０ｍｇ／Ｌ范围内有良好的线性关系,Ｙ＝０．０１６０＋０．０３４０Ｘ,ｒ＝０．９９９１,回收率达９５．０％。日内、日间精密度分别为４．１６％和４．７６％（ｎ＝５）。用所建立的方法测定了患者的血清浓度,结果表明,方法简便、灵敏。     

CE与EP方案治疗小细胞肺癌的临床疗效评价

为观察CE与EP方案治疗小细胞肺癌的近期疗效和毒副反应,对52例小细胞肺癌患者按住院先后顺序,随机分为CE组(卡铂+足叶乙甙)和EP组(顺铂+足叶乙甙),化疗2周期后评价疗效。结果近期疗效方面,CE组CR6例,PR14例,总有效20例(76.9%);EP组CR5例,PR13例,总有效18例(69.2%),两组比较无差别(P>0.05)。在毒副反应方面,CE与EP两组发生Ⅱ度以上的胃肠道反应及骨髓抑制无差别,患者均能耐受。说明CE与EP方案治疗小细胞肺癌均有效,且近期疗效无差别,毒副反应均能耐受,均可作为小细胞肺癌一线化疗方案。     

顺铂、足叶乙甙腹腔灌注治疗癌性腹水35例疗效观察

癌性腹水 35例 ,采用腹腔穿刺抽液后 ,向腹腔内注入顺铂及足叶乙甙 ,观察其疗效及毒副作用。根据国际卫生组织 (WHO)癌性渗液疗效评定标准 ,完全缓解 15例 ,占 4 2 .9% ;部分缓解 7例 ,占 2 0 % ;总有效率 6 2 .9%。可见顺铂、足叶乙甙腹腔灌注治疗癌性腹水效果较好 ,副作用少 ,是一种较为安全有效的方法     

Effect of Kaempferol and Its Glycoside Derivatives on Antioxidant Status of HL-60 Cells Treated with Etoposide

Kaempferol is a well-known antioxidant found in many plants and plant-based foods. In plants, kaempferol is present mainly in the form of glycoside derivatives. In this work, we focused on determining the effect of kaempferol and its glycoside derivatives on the expression level of genes related to the reduction of oxidative stress—NFE2L2, NQO1, SOD1, SOD2, and HO-1; the enzymatic activity of superoxide dismutases; and the level of glutathione. We used HL-60 acute promyelocytic leukemia cells, which were incubated with the anticancer drug etoposide and kaempferol or one of its three glycoside derivatives isolated from the aerial parts of Lens culinaris Medik.—kaempferol 3-O-[(6-O-E-caffeoyl)-β-d-glucopyranosyl-(1→2)]-β-d-galactopyranoside-7-O-β-d-glucuropyranoside (P2), kaempferol 3-O-[(6-O-E-p-coumaroyl)-β-d-glucopyranosyl-(1→2)]-β-d-galactopyranoside-7-O-β-d-glucuropyranoside (P5), and kaempferol 3-O-[(6-O-E-feruloyl)-β-d-glucopyranosyl-(1→2)]-β-d-galactopyranoside-7-O-β-d-glucuropyranoside (P7). We showed that none of the tested compounds affected NFE2L2 gene expression. Co-incubation with etoposide (1 µM) and kaempferol (10 and 50 µg/mL) leads to an increase in the expression of the HO-1 (9.49 and 9.33-fold at 10 µg/mL and 50 µg/mL, respectively), SOD1 (1.68-fold at 10 µg/mL), SOD2 (1.72-fold at 10–50 µg/mL), and NQO1 (1.84-fold at 50 µg/mL) genes in comparison to cells treated only with etoposide. The effect of kaempferol derivatives on gene expression differs depending on the derivative. All tested polyphenols increased the SOD activity in cells co-incubated with etoposide. We observed that the co-incubation of HL-60 cells with etoposide and kaempferol or derivative P7 increases the level of total glutathione in these cells. Taken together, our observations suggest that the antioxidant activity of kaempferol is related to the activation of antioxidant genes and proteins. Moreover, we observed that glycoside derivatives can have a different effect on the antioxidant cellular systems than kaempferol.     

Validated UHPLC–MS/MS assay for quantitative determination of etoposide,gemcitabine, vinorelbine and their metabolites in patients with lung cancer

A fully valid UHPLC–MS/MS method was developed for the determination of etoposide, gemcitabine, vinorelbine and their metabolites (etoposide catechol, 2′,2′‐difluorodeoxyuridine and 4‐O ‐deacetylvinorelbine) in human plasma. The multiple reaction monitoring mode was performed with an electrospray ionization interface operating in both the positive and negative ion modes per compound. The method required only 100 μL plasma with a one‐step simple de‐proteinization procedure, and a short run time of 7.5 min per sample. A Waters ACQUITY UPLC HSS T3 column (2.1 × 100 mm, 1.8 μm) provided chromatographic separation of analytes using a binary mobile phase gradient (A, 0.1% formic acid in acetonitrile, v /v; B, 0.1% formic acid in water, v /v). Linear coefficients of correlation were >0.995 for all analytes. The relative deviation of this method was <10% for intra‐ and inter‐day assays and the accuracy ranged between 86.35% and 113.44%. The mean extraction recovery and matrix effect of all the analytes were 62.07–105.46% and 93.67–105.87%, respectively. This method was successfully applied to clinical samples from patients with lung cancer.     

草药物与人血白蛋白相互作用的分光光度法研究

以曙红Y为光谱探针,采用分光光度法探讨抗癌药物足叶乙甙对人血白蛋白中曙红Y的竞争结合规律,研究足叶乙甙与人血白蛋白的相互作用及结合.结果表明,曙红Y与人血白蛋白以静电作用力为主进行结合,形成电子转移配合物.曙红Y与人血白蛋白结合后,药物足叶乙甙的加入对这种结合产生破坏,争夺并占据人血白蛋白的结合点位,使曙红Y从结合态变成游离态,同时生成新的更为稳定的结合体—人血白蛋白与药物足叶乙甙复合物,其结合比约为7.93molVp16/molHSA.由此说明:足叶乙甙不仅与人血白蛋白存在有效的结合点位,而且具有较好的结合强度和结合容量.这些既是足叶乙甙在人体内贮存和运输的条件,也是其产生抗癌活性的药理基础.     

反相高效液相色谱法测定皮下植入的VP-16血药浓度

试验者为小细胞肺癌患者,于右上臂皮下植入缓释VP-16(又称依托泊苷或鬼臼乙叉苷),按预定时间点采集静脉血并分离出血浆。血浆样品以氯仿萃取,常温下负压挥发至干,然后以流动相溶解,采用反相高效液相色谱法测定。流动相为V(甲醇)∶V(水)=52∶48的溶液,检测波长为UV-228 nm,色谱柱为Lichrosphere C18(250 mmX4.6 mm i.d.,5 μm)。用外标法定量。实验结果表明,该测定方法的检出限为0.02 mg/L,绝对回收率为80.4%,相对回收率为94.7%,日内和日间精密     

Antitumor activity of phaeosphaeride A modified with nitrogen heterocyclic groups

New C(6)-derivatives of natural phaeosphaeride A (PPA) modified with pharmacophoric nitrogen heterocyclic groups have been synthesized. The reaction of 1,2,4-triazole with PPA mesylate produced both the product of the expected substitution of the methanesulfonate group and the PPA derivative with two 1,2,4-triazole groups: at the C(6) atom and the exocyclic C=C bond. The synthesized compounds, with the exception of those containing two 1,2,4-triazole groups, are superior in cytotoxic activity to the original phaeosphaeride and the positive control, etoposide.